The synthesis of anticancer derivatives of (harringtonine) and related model systems is proposed. The objectives behind this investigation are: (1) Develop a versatile synthesis of cephalotaxine and its naturally occurring derivatives. (2) Construct several model systems related to harringtonine in order to "isolate" the active centers (functional groups) giving this alkaloid system antileukemic activity. (3) Prepare several structurally modified versions of cephalotaxine and harringtonine. Allene, 1,4-additions will provide one source of these rare alkaloids as well as, several of the model structures sought for anticancer/antileukemic testing. A second process to be used in preparing the structures mentioned above, combines two well-known reactins, an amide acetal reaction and a Michael (or possibly Mannich) reaction, into one intramolecular conversion. Realization of this process would yield compounds that would be transformed into cephalotaxine (and related structures) by routine chemical conversions. The first phase of such a process has been thoroughly studied by this group. Additional synthetic routes to specific portions of these cephalotaxus structures have been and will be studied. Several harringtonine like compounds, as well as some very novel heterocyclic structures will be screened for antitumor/antileukemic activity on site and at NCI.